The Role of Interleukin-2-Inducible T-cell Kinase in Ulcerative Colitis

A colon affected by ulcerative colitis.
A colon affected by ulcerative colitis.
Investigators attempted to define the role of interleukin-2-inducible T-cell kinase activation in ulcerative colitis.

The activity of interleukin-2-inducible T-cell kinase (ITK), a member of the Tec family of nonreceptor tyrosine kinases, plays a key role in colitis inflammation, according to the results of a study published in Gastroenterology.

Human samples were obtained from patients with ulcerative colitis (n=117), Crohn disease (n=106), and control patients (n=30). Wild-type mice, as well as mice with targeted modifications, were also utilized to analyze ITK activity and the effects of Cyclosporine-A (CsA).

Patients with ulcerative colitis presented with higher ITK activation compared with control patients or patients with Crohn disease. Mice with ITK deficiency demonstrated significant protection from inflammation compared with wild-type mice exposed to the same stimuli. Both sample sources indicate a correlation between ITK activity and severity of inflammation.

Administration of CsA significantly reduced the presence of phosphorylated ITK and reduced mucosal inflammation. Administration of CsA to ITK-deficient mice had minimal effects on inflammation, suggesting that the efficacy of CsA is directly linked to impairing ITK activity.

Future clinical trials are needed, as murine IBD models are limited when applied to human disease. Nonetheless, investigators believe their findings highlight the potential to treat colitis by targeting the activity of ITK.


Lechner K, Mott S, Al-Saifi R, et al. Targeting of the Tec kinase ITK drives resolution of T cell-mediated colitis and emerges as potential therapeutic option in ulcerative colitis. Gastroenterol. Published online July 3, 2021. doi:10.1053/j.gastro.2021.06.072